Accuracy of GFR estimating equations based on creatinine, cystatin C or both in routine care.

BACKGROUND: New equations to estimate glomerular filtration rate based on creatinine (eGFRcr), cystatin C (eGFRcys) or both (eGFRcr-cys) have been developed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and the European Kidney Function Consortium (EKFC). There is a need to evaluate the performance of these equations in diverse European settings to inform implementation decisions, especially among people with key comorbid conditions. METHODS: We performed a cross-sectional study including 6174 adults referred for single-point plasma clearance of iohexol in Stockholm, Sweden, with 9579 concurrent measurements of creatinine and cystatin C. We assessed the performance of the CKD-EPI 2009/2012/2021, EKFC 2021/2023, revised Lund-Malmö (RLM) 2011 and Caucasian, Asian, Pediatric and Adult (CAPA) 2014 equations against measured GFR (mGFR). RESULTS: Mean age was 56 years, median mGFR was 62 mL/min/1.73 m2 and 40% were female. Comorbid conditions were common: cardiovascular disease (30%), liver disease (28%), diabetes (26%) and cancer (26%). All eGFRcr-cys equations had small bias and P30 (the percentage of estimated values within 30% of mGFR) close to 90%, and performed better than eGFRcr or eGFRcys equations. Among eGFRcr equations, CKD-EPI 2009 and CKD-EPI 2021 showed larger bias and lower P30 than EKFC 2021 and RLM. There were no meaningful differences in performance across eGFRcys equations. Findings were consistent across comorbid conditions, and eGFRcr-cys equations showed good performance in patients with liver disease, cancer and heart failure. CONCLUSIONS: In conclusion, eGFRcr-cys equations performed best, with minimal variation among equations in this Swedish cohort. The lower performance of CKD-EPI eGFRcr equations compared with EKFC and RLM may reflect differences in population characteristics and mGFR methods. Implementing eGFRcr equations will require a trade-off between accuracy and uniformity across regions.

The EKFC equation outperforms the CKD-EPI and CKiD equations for GFR estimation in adolescent and young adult kidney transplant patients.

AIM: This study evaluated the bias and accuracy of the CKD-EPI/CKiD and EKFC equations compared with the reference exogenous tracer-based assessment of glomerular filtration rate (GFR) in adult and pediatric patients according to their renal transplant status. METHODS: We assessed the bias and P30 accuracy of the CKD-EPI/CKiD and EKFC equations compared with iohexol-based GFR measurement. RESULTS: In the overall population (n = 59), the median age was 29 years (IQR, 16.0-46.0) and the median measured GFR was 73.9 mL/min/1.73m2 (IQR, 57.3-84.6). Among non-kidney transplant patients, the median was 77.7 mL/min/1.73m2 (IQR, 59.3-86.5), while among kidney transplant patients, it was 60.5 mL/min/1.73m2 (IQR, 54.2-66.8). The bias associated with the EKFC and CKD-EPI/CKiD equations was significantly higher among kidney transplant patients than among non-kidney transplant patients, with a difference between medians (Hodges-Lehmann) of +10.4 mL/min/1.73m2 (95% CI, 2.2-18.9; p = .02) for the EKFC and +12.1 mL/min/1.73m2 (95% CI, 4.2-21.4; p = .006) for the CKD-EPI/CKiD equations. In multivariable analysis, kidney transplant status emerged as an independent factor associated with a bias of >3.4 mL/min/1.73m2 (odds ratio, 7.7; 95% CI, 1.4-43.3; p = .02) for the EKFC equation and a bias of >13.4 mL/min/1.73m2 (odds ratio, 15.0; 95% CI, 2.6-85.7; p = .002) for the CKD-EPI/CKiD equations. CONCLUSION: In our study, which included adolescent and young adult kidney transplant patients, both the CKD-EPI/CKiD and EKFC equations tended to overestimate the measured glomerular filtration rate, with the EKFC equation exhibiting less bias. Renal transplant status significantly influenced the degree of estimation bias.

Application of the European Kidney Function Consortium Equation to Estimate Glomerular Filtration Rate: A Comparison Study of the CKiD and CKD-EPI Equations Using the Korea National Health and Nutrition Examination Survey (KNHANES 2008-2021).

Background and Objectives: The European Kidney Function Consortium (EKFC) equation has been newly proposed for estimating glomerular filtration rate (eGFR) across the spectrum of age. We compared the EKFC equation with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in a large-scale Korean population. Materials and Methods: Using the representative Korean health examination data, the Korea National Health and Nutrition Examination Survey (KNHANES 2008-2021), the records of 91,928 subjects (including 9917 children) were analyzed. We compared the EKFC equation with CKiD, CKD-EPI 2009, and CKD-EPI 2021 equations and investigated their agreement across GFR categories. Results: In the total population, the CKD-EPI 2021 equation yielded the highest eGFR value, followed by the CKD-EPI 2009 and EKFC equations. In children, the distribution of eGFR differed significantly between the EKFC and CKiD equations (p < 0.001), with a wider range of eGFR values found with the CKiD equation. Each equation showed weak or moderate agreement on the frequency of the GFR category (κ = 0.54 between EKFC and CKD-EPI 2021; κ = 0.77 between EKFC and CKD-EPI 2009). The eGFR values found by the EKFC equation showed high or very high correlations with those by the CKiD, CKD-EPI 2009, and CKD-EPI 2021 equations (r = 0.85, 0.97, and 0.97, respectively). As eGFR values increased, bigger differences were observed between equations. Conclusions: This large-scale study demonstrates that the EKFC equation would be applicable across the entire age spectrum in Asian populations. It also underscores that national kidney health would be highly affected by an eGFR equation being implemented. Additional investigation and more caution would be warranted for the transition of eGFR equations.

Removing race from the CKD-EPI equation and its impact on prognosis in a predominantly White European population.

BACKGROUND: While American nephrology societies recommend using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rate (eGFR) equation without a Black race coefficient, it is unknown how this would impact disease distribution, prognosis and kidney failure risk prediction in predominantly White non-US populations. METHODS: We studied 1.6 million Stockholm adults with serum/plasma creatinine measurements between 2007 and 2019. We calculated changes in eGFR and reclassification across KDIGO GFR categories when changing from the 2009 to 2021 CKD-EPI equation; estimated associations between eGFR and the clinical outcomes kidney failure with replacement therapy (KFRT), (cardiovascular) mortality and major adverse cardiovascular events using Cox regression; and investigated prognostic accuracy (discrimination and calibration) of both equations within the Kidney Failure Risk Equation. RESULTS: Compared with the 2009 equation, the 2021 equation yielded a higher eGFR by a median [interquartile range (IQR)] of 3.9 (2.9-4.8) mL/min/1.73 m2, which was larger at older age and for men. Consequently, 9.9% of the total population and 36.2% of the population with CKD G3a-G5 was reclassified to a higher eGFR category. Reclassified individuals exhibited a lower risk of KFRT, but higher risks of all-cause/cardiovascular death and major adverse cardiovascular events, compared with non-reclassified participants of similar eGFR. eGFR by both equations strongly predicted study outcomes, with equal discrimination and calibration for the Kidney Failure Risk Equation. CONCLUSIONS: Implementing the 2021 CKD-EPI equation in predominantly White European populations would raise eGFR by a modest amount (larger at older age and in men) and shift a major proportion of CKD patients to a higher eGFR category. eGFR by both equations strongly predicted outcomes.

The new, race-free, Chronic Kidney Disease Epidemiology Consortium (CKD-EPI) equation to estimate glomerular filtration rate: is it applicable in Europe? A position statement by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM).

The EFLM recommends not to implement the race-free Chronic Kidney Disease Epidemiology Consortium (CKD-EPI) equation in European laboratories and to keep the 2009 version of the CKD-EPI equation, without applying a race correction factor. This recommendation is completely in line with a recent Editorial published by the European Renal Association who has also proposed to change to a novel equation only when it has considerably better performance, trying to reach global consensus before implementing such a new glomerular filtration rate (GFR) estimation equation. In Europe, this equation could be for instance the new European Kidney Function Consortium (EKFC) equation, which is population-specific, developed from European cohorts and accurate from infants to the older old. Beyond serum creatinine, the estimating equations based on cystatin C will probably gain in popularity, especially because cystatin C seems independent of race. Finally, we must keep in mind that all GFR equations remain an estimation of GFR, especially rough at the individual level. Measuring GFR with a reference method, such as iohexol clearance, remains indicated in specific patients and/or specific situations, and here also, the role of the clinical laboratories is central and should still evolve positively in the future.

A study indicates an essential link between a mild deterioration in excretory kidney function and the risk of neutropenia during cancer chemotherapy.

PURPOSE: Neutropenia, defined as a number of neutrophils in patients' blood specimen lower than 1500 cells/µm3, is a common adverse event during myelosuppressive oncological chemotherapy, predisposing to febrile neutropenia (FN). Patients with coexisting moderate-to-severe chronic kidney disease (CKD) have an increased risk of FN, included in the guidelines for the primary prophylaxis of FN. However, this does not include mild kidney function impairment with estimated glomerular filtration rate (eGFR) 60-89 ml/min/1.73 m2. This prospective study analyzed the risk of neutropenia in patients on chemotherapy without indication for the primary prophylaxis of FN. METHODS: The study enrolled 38 patients starting chemotherapy, including 26 (68.4%) patients aged 65 years or more. The median duration of follow-up was 76 days. The methodology of creatinine assessment enabled the use of the recommended CKD-EPI formula for identifying patients with a mild reduction of glomerular filtration. RESULTS: Sixteen (42.1%) patients developed at least G2 neutropenia without episodes of FN. Only five (13.1%) patients had eGFR < 60 ml/min/1.73 m2, while 15 (62.5%) eGFR < 90 ml/min/1.73 m2. The relative risk of neutropenia in patients with impaired eGFR was over six times higher than in patients with eGFR > 90 ml/min/1.73 m2 (RR = 6.08; 95%CI:1.45-27.29; p < 0.01). CONCLUSIONS: Our observation indicates that even a mild reduction in eGFR is a risk factor for the development of neutropenia and a potential risk factor for FN. Authors are advised to check the author instructions for the journal they are submitting to for word limits and if structural elements like subheadings, citations, or equations are permitted.

Lower range of serum uric acid level increases risk of rapid decline of kidney function in young and middle-aged adults: the Yuport Medical Checkup Center Study.

BACKGROUND: The effect of low serum uric acid (sUA) levels on kidney function is unclear. This study aimed to clarify the relationship between low sUA levels and the rapid decline in kidney function. METHODS: We examined the relationship between sUA levels and kidney function decline in health check-up examinees. A total of 10,547 participants were enrolled using data from the Yuport Medical Checkup Center Study between 1998 and 2002 for baseline and data from 2002 to 2006 as the follow-up period in Japan. According to sUA level (mg/dL), we classified the participants into the following six groups: (1) 2.0-2.9 (n = 247), (2) 3.0-3.9 (n = 1457), (3) 4.0-4.9 (n = 2883), (4) 5.0-5.9 (n = 2899), (5) 6.0-6.9 (n = 2010), and (6) 7.0-7.9 (n = 1,051). The relationship between sUA level and rapid decline in estimated glomerular filtration rate (ΔeGFR ≥ 3 mL/min/1.73 m2/year) was examined using a logistic regression model. RESULTS: During study period (5.4 ± 1.6 years), the incidence of rapid eGFR decline for the respective sUA groups (2.0-2.9, 3.0-3.9, 4.0-4.9, 5.0-5.9, 6.0-6.9, 7.0-7.9) were as follows: 4.5%, 4.0%, 2.4%, 3.3%, 3.1%, 3.4%. The crude and adjusted odds ratios (OR) for rapid eGFR decline were significantly higher in the 2.0-2.9 (OR:1.93 and 1.86) and 3.0-3.9 (OR:1.72 and 1.73) groups than in the 4.0-4.9 groups (reference). Stratified analysis of age differences revealed that the detrimental effect of low sUA was not evident in older adults (age ≥ 65 years). CONCLUSION: A lower normal sUA level is related to an increased risk for a rapid decline in kidney function.

Sex-specific association of body mass index and fatty liver index with prevalence of renal hyperfiltration: a cross sectional study using Japanese health check-up data.

BACKGROUND: The relationship between obesity and nonalcoholic fatty liver disease and renal hyperfiltration is controversial. This study aimed to assess the correlations of body mass index and fatty liver index, respectively, with renal hyperfiltration in non-diabetic subjects, considering age, sex, and body surface area. METHODS: This cross-sectional study assessed the Japanese health check-up data (FY2018) of 62,379 non-diabetic individuals from a health insurance database. Renal hyperfiltration is the ≥ 95th percentile of estimated glomerular filtration rate (derived by Chronic Kidney Disease Epidemiology Collaboration formula) by gender and age in healthy subjects. After adjusting for potential confounders, multiple logistic regression models were applied to evaluate the correlation of renal hyperfiltration with body mass index categories and fatty liver index (10 equal parts). RESULTS: A negative and positive correlation, respectively, were noted when the body mass index was < 21 and ≥ 30 in women; however, a positive correlation was noted for BMI < 18.5 and ≥ 30 in men. Renal hyperfiltration prevalence increased when fatty liver index increased for both sexes; the cutoff value for fatty liver index was 14.7 for women and 30.4 for men. CONCLUSIONS: Body mass index and renal hyperfiltration correlated linearly in women; however, in men, the correlation was U-shaped; therefore, differing by sex. However, fatty liver index correlated linearly with renal hyperfiltration in both sexes. Non-alcoholic fatty liver disease might be associated with renal hyperfiltration; Fatty liver index is a simple marker that can be obtained from health check-ups. Since a high fatty liver index correlated with renal hyperfiltration, it may be beneficial to monitor the renal function in such a population.

Validation of the EKFC equation for glomerular filtration rate estimation and comparison with the Asian-modified CKD-EPI equation in Chinese chronic kidney disease patients in an external study.

OBJECTIVES: The aim of this study is to determine whether new European Kidney Function Consortium (EKFC) equation is more applicable than Asian-modified CKD-EPI equation in clinical practice, having a higher accuracy in estimating GFR in our external CKD population. METHODS: We calculated estimated GFREKFC and GFRCKD-EPI independently using the EKFC and Asian-modified CKD-EPI formulas, respectively. The clinical diagnostic performance of the two equations was assessed and compared by median bias, precision, accuracy (P30) and so on, using 99mTc-DTPA dual plasma sample clearance method as a reference method for GFR measurement (mGFR). The equation that met the following targets was superior: (1) median bias within ± 3 mL/min/1.73 m2; (2) P30 > 75%; and (3) better precision and 95% limits of agreement in Bland-Altman analysis. RESULTS: Totally, 160 CKD patients were recruited in our external cohort. GFREKFC was highly related to mGFR, with a regression equation of GFREKFC=mGFR × 0.87 + 5.27. Compared with the Asian-modified CKD-EPI equation, EKFC equation demonstrated a wider median bias (-1.64 vs. 0.84 mL/min/1.73 m2, p < 0.01) that was within 3 mL/min/1.73 m2 and not clinically meaningful. Furthermore, the precision (12.69 vs. 12.72 mL/min/1.73 m2, p = 0.42), 95% limits of agreement in Bland-Altman analysis (42.4 vs. 44.4 mL/min/1.73 m2) and incorrect reclassification index of the two target equations were almost identical. Although, EKFC equation had a slightly better P30 (80.0% vs. 74.4%, p = 0.01). CONCLUSIONS: The overall performance of EKFC equation is acceptable. There is no clinically meaningful difference in the performance of the Asian-modified CKD-EPI and EKFC equations within the limits imposed by the small sample size.

Performance of the 2021 Race-Free CKD-EPI Creatinine- and Cystatin C-Based Estimated GFR Equations Among Kidney Transplant Recipients.

RATIONALE & OBJECTIVE: Race-free estimated glomerular filtration rate (eGFR) equations incorporating creatinine with and without cystatin C were recently developed and recommended for routine use. However, the performance of these equations among kidney transplant recipients (KTRs) remains unknown. STUDY DESIGN: Cross-sectional study to validate the 2021 race-free Chronic Kidney Disease (CKD) Epidemiology Collaboration (CKD-EPI) eGFR equation based on creatinine alone (eGFRcr) or based on creatinine and cystatin C (eGFRcr-cys) among KTRs. SETTING & PARTICIPANTS: KTRs in stable condition (N = 415) from Canada and New Zealand with same-day measurements of creatinine, cystatin C, and glomerular filtration rate (GFR) using radiolabeled diethylenetriaminepentaacetic acid. TESTS COMPARED: The 2009 CKD-EPI eGFRcr, 2021 CKD-EPI eGFRcr, 2012 CKD-EPI eGFRcr-cys, 2021 CKD-EPI eGFRcr-cys, 2012 CKD-EPI eGFRcys, and Modification of Diet in Renal Disease (MDRD) Study eGFR equations were compared with measured GFR. OUTCOMES: Bias, precision, accuracy, and correct classification by CKD stage. Bias was defined as the difference between estimated and measured GFR. Precision was represented by the interquartile range. Accuracy was defined as the percentages of participants with eGFRs within 10%/20%/30% (P10/P20/P30) of measured GFR, root mean square error, and mean absolute error. RESULTS: 87% of patients studied were White, 3% Black, and 10% other races. Mean measured GFR was 53 ± 19 (SD) mL/min/1.73 m2. The 2009 and 2021 CKD-EPI eGFRcr equations demonstrated similar median bias (-2.3 vs -0.2 mL/min/1.73 m2, respectively), precision (14.5 vs 14.9 mL/min/1.73 m2), and accuracy (P10/P20/P30, 32%/65%/84% vs 33%/63%/84%). The 2012 and 2021 CKD-EPI eGFRcr-cys equations also demonstrated similar median bias (-3.6 vs 0.3 mL/min/1.73 m2, respectively), precision (13.3 vs 14.3 mL/min/1.73 m2), and accuracy (P10/P20/P30, 32%/63%/80% vs 32%/67%/83%). No clear difference in performance was detected between the 2021 CKD-EPI eGFRcr and eGFRcr-cys equations among KTRs. The proportion of correct classification by CKD stage was similar across all eGFR equations. LIMITATIONS: Moderate sample size, few patients had a GFR <30 mL/min/1.73 m2, and the large majority of patients were White. CONCLUSIONS: Among KTRs, the 2021 race-free CKD-EPI eGFR equations perform similarly to the previous CKD-EPI equations that included race correction terms. No significant difference in performance was observed between the 2021 CKD-EPI eGFRcr and eGFRcr-cys equations in the kidney transplant population.

Renal safety of zoledronic acid for osteoporosis in adults 75 years and older.

Our study examined renal function change in older adults with osteoporosis, treated with zoledronic acid. Risk of nephrotoxicity was low. Future studies are needed to evaluate use of zoledronic acid in patients with a CCr < 35 mL/min, as patients may be inappropriately excluded from its use. INTRODUCTION: Zoledronic acid (ZA) is used for the treatment of osteoporosis (OP). Renal impairment is a known risk factor for the rare occurrence of nephrotoxicity after ZA infusions, leading to use being contraindicated below creatinine clearance (CCr) of 35 mL/min. Our aims are to examine changes in serum creatinine (SCr) after infusions, capture frequency of acute kidney injury (AKI), and describe baseline kidney function estimates in adults 75 years and older being treated for OP. METHODS: This was a retrospective, cross-sectional, pre-post analysis that examined change in SCr before and after ZA infusions. The primary outcome was assessed using a paired Student t-test. Incidence of AKI within 1 year following infusions was noted and patient-specific factors were collected. RESULTS: Five hundred fifty-eight ZA infusions in 327 patients met criteria. Mean SCr decreased by 0.01 mg/dL in the year following ZA infusions (p = 0.005). AKI occurred in 1.4% of patients and all had CCr > 45 mL/min. 4.5% of patients had CCr < 35 mL/min and none experienced an AKI. CONCLUSION: There was no clinically relevant change in SCr after ZA infusions. Risk of nephrotoxicity was low and similar to risk seen in randomized trials occurring in younger patients. Kidney function estimates were dramatically lower using the Cockcroft-Gault (CG) equation in comparison to CKD-EPI. We believe use of the CG equation in this population may be inappropriately limiting our ability to use ZA for treatment of OP in older adults but more evidence is necessary.

Carboplatin dose calculations for patients with lung cancer: significant dose differences found depending on dosing equation choice.

BACKGROUND: Carboplatin is the backbone cytotoxic agent for many chemotherapy regimens for lung cancer. Dosing of carboplatin is complicated due to its relationship to renal function and narrow therapeutic index. Overestimation of renal function may lead to supratherapeutic dosing and toxicity, while underestimation may lead to underdosing and therapeutic failure. Although the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations have higher accuracy in estimating glomerular filtration rate (eGFR), the Cockcroft Gault (CG) formula has been historically used for carboplatin dosing internationally. METHODS: We compared these formulae to identify patient profiles that were associated with significant carboplatin dose variation by retrospectively analysing the carboplatin dosing of 96 patients with lung cancer. Carboplatin doses were calculated using eGFR generated by MDRD, CKD-EPI 2009 and CKD-EPI 2021 equations. These three hypothetical doses were compared to actual CG-based doses prescribed. RESULTS: MDRD and CKD-EPI equations resulted in comparable carboplatin doses; however, CG doses diverged markedly with up to 17% of the patients receiving a carboplatin dose that was at least 20% higher than a non-CG formula would have predicted, and 20% received a dose that was at least 20% lower than a non-CG formula would have predicted. Our data suggest CG use overestimates kidney function in patients with a higher bodyweight and body surface area (BSA) while underestimating it in patients with a lower bodyweight and BSA. Importantly, we demonstrate potential real-world benefit as CKD-EPI predicted lower doses for patients whose (CG-derived) carboplatin dose was later reduced following clinical assessment prior to infusion. CONCLUSIONS: We have therefore confirmed significant differences in carboplatin dosing depending on the equation used in our modern patient population and suggest that use of CKD-EPI provides the most clinically appropriate carboplatin dosing and should be implemented as the new standard of care internationally.

Assessment of pre-donation glomerular filtration rate: going back to basics.

The 2017 version of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines is the most recent international framework for the evaluation and care of living kidneys donors. Along with the call for an integrative approach evaluating the long-term end-stage kidney disease risk for the future potential donor, several recommendations are formulated regarding the pre-donation glomerular filtration rate (GFR) adequacy with no or little consideration for the donor candidate's age or for the importance of using reference methods of GFR measurements. Herein, we question the position of the KDIGO guidelines and discuss the rationale and modalities for a more basic, but no less demanding GFR evaluation enabling a more efficient selection of potential kidney donors.

Long-term outcomes of transplant kidneys donated after circulatory death.

BACKGROUND: Donation after circulatory death (DCD) represents up to 40% of used kidney grafts. While studies have shown similar outcomes compared with donation after brain death (DBD) in the short term and mid-term, no data on long-term outcomes exist. METHODS: We retrospectively analysed patients transplanted at our institution between January 1985 and March 2000. All DCD recipients were matched one-to-one with patients transplanted with DBD grafts during this period according to sex, age and year of transplantation and followed up until December 2020. During this period, 1133 kidney transplantations were performed, of which 122 were with a DCD graft. RESULTS: The median graft survival after 35 years of follow-up was 23 years [277 months {95% confidence interval (CI) 182-372}] in DBD recipients and 24.5 years [289 months (95% CI 245-333)] in DCD recipients (P = 0.65; hazard ratio 0.91). Delayed graft function occurred in 47 patients in the DCD group compared with 23 in the DBD group (P < 0.001), albeit without a significant long-term outcome difference in graft or patient survival. We could not show any difference in graft function in terms of creatinine levels (133 versus 119 µmol/L), proteinuria (370 versus 240 mg/24 h) and glomerular filtration rate slope (-0.6 versus -0.3 mL/min/year) between the two groups for graft survival >20 years. CONCLUSIONS: This is the first study to show similar graft survival and function in DCD kidneys compared with DBD kidneys after 35 years of follow-up. DCD grafts are a valuable resource and can be utilized in the same way as DBD grafts.

Calculation of the estimated glomerular filtration rate using the 2021 CKD-EPI creatinine equation and whole blood creatinine values measured with Radiometer ABL 827 FLEX.

OBJECTIVES: Estimated glomerular filtration rate (eGFR) can be calculated using serum/plasma creatinine measured with automated chemistry analyzers. It is unclear whether eGFR can be calculated using creatinine values measured in whole blood (WB creatinine). The aim of this study is to determine the comparability between the eGFR calculated using WB creatinine and plasma creatinine. METHODS: Blood samples from 1,073 patients presented to the emergency department (ED), perioperative areas, intensive care unit (ICU) or nuclear medicine were used to determine the accuracy of WB creatinine. For each sample, WB creatinine was first measured with Radiometer ABL827 FLEX blood gas analyzer, then plasma creatinine was measured with Roche Cobas702 chemistry analyzer after samples were centrifuged. In a subset of 247 samples with the information of age and sex, whole blood eGFR (WB eGFR) and plasma eGFR were calculated using WB creatinine and plasma creatinine and the 2021 chronic kidney disease epidemiology collaboration (CKD-EPI) creatinine equation, respectively. RESULTS: WB creatinine correlated with plasma creatinine linearly with a slope of 1.06 and an intercept of -0.01. The coefficient of determination (R2) was 0.99. WB eGFR correlated with plasma eGFR linearly with a slope of 0.95, intercept of -1.63, and R2 of 0.97. Comparing to plasma eGFR, the sensitivity and specificity for WB eGFR to identify those with high risk (eGFR<30 mL/min/1.73 m2) and low risk (eGFR>45 mL/min/1.73 m2) for kidney injuries was 100 and 92.2%, respectively. The overall concordance in classifying the four stages of kidney damage between WB eGFR and plasma eGFR was 87.9%. CONCLUSIONS: WB creatinine measured with Radiometer ABL827 Flex can be used to calculate eGFR using the 2021 CKD-EPI creatinine equation. The sensitivity and specificity for WB eGFR to identify those with high and low risks for potential kidney injuries are acceptable in patients needing rapid assessment of their kidney functions.

Impact of Removing the Race Coefficient in Renal Function Estimate Equations on Drug Dosage Recommendations.

BACKGROUND: The appropriateness of including the race coefficient in glomerular filtration rate (GFR) equations in Black patients is debated, and the impact on drug dosing is unknown. OBJECTIVE: This study explored the impact of removing the race coefficient on drug dosing in Black patients in comparison to conventional methods. METHODS: This was a retrospective study of hospitalized patients who self-identified as Black/African American and were prescribed an antimicrobial that includes renal dosage recommendations in the product labeling. The primary end point was the discordance between drug dosing recommendations derived by body surface area deindexed GFR estimated by the CKD-EPI equation (Chronic Kidney Disease Epidemiology study) with and without race versus recommendations derived from Cockcroft-Gault (CG). RESULTS: A total of 210 Black patients were included. There was an 18% rate of discordance when GFR was estimated with the race coefficient (GFR w/Race) versus without the race coefficient (GFR w/out Race). GFR w/out Race had a higher level of agreement with dosing by creatinine clearance (CrCl; κ = 0.779) than GFR w/Race versus CrCl (κ = 0.651). GFR w/out Race had less within-patient difference than GFR w/Race in comparison to CrCl (mean difference: -6.3 vs -18.0 mL/min). CONCLUSIONS AND RELEVANCE: This represents the first report to examine the removal of the race coefficient and its implication on drug dose discordance. GFR w/out Race had a higher level of agreement and less drug dose discordance than GFR w/Race, in comparison to CrCl estimates. If GFR equations are considered comparable to CrCl for the purposes of guiding drug dosing, GFR w/out Race should be considered.

Should the CKD EPI Equation Be Used for Estimation of the Glomerular Filtration Rate in Obese Subjects?

INTRODUCTION: The pandemic of obesity is strongly related to increase of chronic kidney disease (CKD) prevalence. The currently recommended CKD epidemiology collaboration (CKD EPI) equation has several serious limitations, particularly in obese subjects who have high body surface area (BSA). The aim of our study was to analyze differences in the prevalence of CKD between CKD EPI and de-indexed equations where individual BSA was used. METHODS: In a total of 2,058 subjects (random sample from a general rural population, 29.65% obese), BSA was estimated using DuBois and DuBois and Moesteller equations and included into the de-indexed equations (CKD DBi, CKD Mi). CKD was classified according to the KDIGO guidelines, and glomerular hyperfiltration (GHF) was defined as 95th percentile, according to the gender and age decade. RESULTS: In obese subjects, prevalence of CKD was significantly higher with CKD EPI than with CKD DBi and CKD Mi equations (9.5%, 6.1%, 5.3%, respectively; p < 0.001), while prevalence of GHF was significantly lower (3.8%, 12.3%, 12.8%, respectively; p < 0.001). Opposite results were observed in subjects with a body mass index <25 kg/m2 for CKD (5%, 7.1%, 7.2%; p = 0.07) and GHF prevalence (6.1%, 1%, 0.6%; p < 0.001). DISCUSSION/CONCLUSIONS: The prevalence of CKD is overestimated, and the prevalence of GHF is underestimated in obese subjects using the CKD EPI equation, i.e., the CKD EPI equation is unreliable in one-third of the population. De-indexed equations should be recommended instead of the CKD EPI equation in epidemiological studies until direct measurement of the glomerular filtration rate becomes more available.

High prevalence of chronic kidney disease of unknown etiology among workers in the Mesoamerican Nephropathy Occupational Study.

BACKGROUND: Mortality from chronic kidney disease of unknown etiology (CKDu) is extremely high along the Pacific coast of Central America, particularly among sugarcane workers. The Mesoamerican Nephropathy Occupational Study (MANOS) is a prospective cohort study of CKDu among agricultural and non-agricultural workers in El Salvador and Nicaragua. The objective of this manuscript is to describe the MANOS cohort recruitment, baseline data collection, and CKDu prevalence after two rounds. METHODS: Workers with no known diabetes, hypertension, or CKD were recruited from sugarcane, corn, plantain, brickmaking, and road construction industries (n = 569). Investigators administered questionnaires, collected biological samples, and observed workers for three consecutive workdays at the worksite. Serum specimens were analyzed for kidney function parameters, and used to calculate estimated glomerular filtration rate (eGFR). At six months, serum was collected again prior to the work shift. CKD at baseline is defined as eGFR ≤ 60 ml/min/1.73m2 at both timepoints. Age-standardized prevalence was calculated by industry, country, and demographic measures. Kidney function parameters were compared by CKD status. RESULTS: Prevalence of CKD at baseline was 7.4% (n = 42). Age-standardized prevalence was highest in Salvadoran sugarcane (14.1%), followed by Salvadoran corn (11.6%), and Nicaraguan brickmaking (8.1%). Nicaraguan sugarcane had the lowest prevalence, likely due to kidney function screenings prior to employment. CONCLUSION: Despite efforts to enroll participants without CKD, our identification of prevalent CKD among agricultural and non-agricultural workers in the MANOS cohort indicates notable kidney disease in the region, particularly among sugarcane workers.

Association of renal impairment with cognitive dysfunction in the Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA).

INTRODUCTION: Chronic kidney disease (CKD) is a recognized risk factor for cognitive impairment. Identification of those at greatest risk of cognitive impairment may facilitate earlier therapeutic intervention. This study evaluated associations between estimated glomerular filtration rate (eGFR) and cognitive function in the Northern Ireland Cohort for the Longitudinal Study of Ageing. METHODS: Data were available for 3412 participants ≥50 years of age living in non-institutionalized settings who attended a health assessment between February 2014 and March 2016. Measures of serum creatinine (SCr) and cystatin C (cys-C) were used for eGFR. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE). RESULTS: Following adjustment for potential confounders, a single unit decrease in eGFR was significantly associated with reduced cognitive function defined by an MMSE ≤24/30 {eGFR calculated using serum cys-C [eGFRcys]: ß = -0.01 [95% confidence interval (CI) -0.001 to -0.01], P = 0.01} and MoCA <26/30 [ß = -0.01 (95% CI -0.002 to -0.02), P = 0.02]. Similarly, CKD Stages 3-5 were also associated with a moderate increase in the odds of cognitive impairment (MMSE ≤24) following adjustment for confounders [eGFRcys: odds ratio 2.73 (95% CI 1.38-5.42), P = 0.004]. CONCLUSIONS: Decreased eGFRcys was associated with a significantly increased risk of cognitive impairment in a population-based cohort of older adults. However, there was no evidence of an association between cognitive impairment and the more commonly used eGFR calculated using SCr. eGFRcys may offer improved sensitivity over eGFRcr in the determination of renal function and associated risk of cognitive impairment.

Performance of the various serum creatinine-based GFR estimating equations in pediatric kidney transplant recipients, stratified by age and CKD staging.

BACKGROUND: Numerous equations are used to estimate glomerular filtration rate (eGFR), based on serum creatinine (SCr), demographic and anthropometric data, none established in pediatric kidney transplant recipients. This study aimed to validate the available SCr-based eGFR equations in comparison with a measured (mGFR), stratified by chronic kidney disease (CKD) stage and age at the time of testing. METHODS: One hundred twenty-seven pediatric kidney transplant recipients with 411 mGFR values (plasma clearance of iothalamate) were enrolled in this retrospective study. The bias, precision, and accuracy (percentage of estimates within 10% and 30% of mGFR) of five SCr eGFR equations (original Schwartz, CKiDSCr equation, Pottel, Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)) were assessed. RESULTS: Height-independent Pottel equation performed well across all the categories of age and CKD staging. CKiDSCr equation performed well in CKD stages II-V. The CKiDSCr equation had a lower bias in children < 15 years of age, while MDRD and CKD-EPI equations had less bias in children > 15 years. Overall, both the Pottel and CKiDSCr equations had high accuracy (80%) and low bias (< 5 ml/min/1.73 m2). In contrast, the original Schwartz, MDRD, and CKD-EPI equations displayed high bias and low precision/accuracy. CONCLUSIONS: Given their low bias and high accuracy across ages and CKD stages, the Pottel or the CKiDSCr equation is better to assess eGFR in pediatric kidney transplant recipients. The Pottel equation outperformed other eGFR equations in adolescents.